Hyperglycemia Induces Osteoclastogenesis and Bone Destruction Through the Activation of Ca2+/Calmodulin-Dependent Protein Kinase II

  • Yanxin Shen
  • Shujuan Guo
  • Guoqing Chen
  • Yi Ding
  • Yafei WuEmail author
  • Weidong TianEmail author
Original Research


Hyperglycemia induces osteoclastogenesis and bone resorption through complicated, undefined mechanisms. Ca2+/calmodulin-dependent protein kinase II (CaMKII) promotes osteoclastogenesis, and could be activated by hyperglycemia. Here, we investigated whether CaMKII is involved in hyperglycemia-induced osteoclastogenesis and subsequent bone resorption. Osteoclast formation, bone resorption, CaMKII expression and phosphorylation were measured under high glucose in vitro and in streptozotocin-induced hyperglycemia rats with or without CaMKII inhibitor KN93. The results showed that 25 mmol/L high glucose in vitro promoted cathepsin K and tartrate-resistant acid phosphatase expression (p < 0.05) and osteoclast formation (p < 0.01) associated with enhancing β isoform expression (p < 0.05) and CaMKII phosphorylation (p < 0.001). Hyperglycemia promoted the formation of osteoclasts and resorption of trabecular and alveolar bone, and inhibited sizes of femur and mandible associated with enhanced CaMKII phosphorylation (p < 0.001) in rats. All these changes could be alleviated by KN93. These findings imply that CaMKII participates not only in hyperglycemia-induced osteoclastogenesis and subsequent bone resorption, but also in the hyperglycemia-induced developmental inhibition of bone.


Hyperglycemia Type 1 diabetes mellitus Osteoclast Ca2+/calmodulin-dependent protein kinase II Bone resorption 



The work was supported by the National Key Research and Development Program of China (2017YFA0104800) and National Natural Science Foundation of China (Grant No. 81200792).

Author Contributions

YS, SG, YW and WT designed the study; YS and SG performed the experiments; YS and GC analyzed the data; YS prepared the first draft of the paper; YS, SG, YD, YW and WT revised the paper. All authors reviewed and approved the final version. WT is guarantor. All authors agree to be accountable for the work and to ensure that any questions relating to the accuracy and integrity of the paper are investigated and properly resolved.

Compliance with Ethical Standards

Conflict of interest

Yanxin Shen, Shujuan Guo, Guoqing Chen, Yi Ding, Yafei Wu and Weidong Tian declare no conflict of interest.

Human and Animal Rights and Informed Consent

All procedures performed in studies involving animals were in accordance with the ethical standards of the ethics committee of Sichuan University.


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of StomatologySichuan UniversityChengduPeople’s Republic of China
  2. 2.National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of StomatologySichuan UniversityChengduPeople’s Republic of China
  3. 3.Department of Periodontics, West China Hospital of StomatologySichuan UniversityChengduPeople’s Republic of China
  4. 4.Department of Oral and Maxillofacial Surgery, West China Hospital of StomatologySichuan UniversityChengduPeople’s Republic of China

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